Anti-CD3 monoclonal antibody-mediated cytotoxicity occurs through an interleukin-2-independent pathway in CD3+ large granular lymphocytes.
The mechanism of induction of cytotoxicity produced by anti-CD3 monoclonal antibody (MoAb) was studied in four patients with CD3+ large granular lymphocyte (LGL) leukemia. Anti-CD3 MoAb treatment resulted in increased target cell binding and increased granule formation. After activation, leukemic LGL remained Tac-, with the exception of a patient with CD4+ LGL leukemia. Radiolabeled interleukin-2 (IL-2) binding studies demonstrated that treatment with anti-CD3 MoAb resulted in upregulation of the number of p75 intermediate affinity IL-2 receptor sites per cell. Northern blot hybridization analysis showed expression of gamma-interferon gene transcripts 24 to 48 hours after activation. There was no evidence for expression of IL-2 messenger RNA or secretion of IL-2 after activation. Anti-CD3 MoAb and IL-2 provide different signals for activation of CD3+ LGL. Induction of cytotoxicity produced by anti-CD3 MoAb in leukemic CD3+ LGL is not associated with IL-2 production.
Loughran
T P
TP
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Aprile
J A
JA
Ruscetti
F W
FW
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology* / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology*; D015152:Blotting, Northern; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008854:Microscopy, Electron; D010641:Phenotype
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2